Genotoxicity studies on urine and bone marrow samples of rats bearing transplanted nephroma.

Abstract

It was demonstrated earlier that urine of rats bearing transplanted mesoblastic nephroma had high mutagenic activity in Salmonella typhimurium, which could not be detected in serum samples of the same animals. In this paper, cytogenetic alterations are discussed and the lack of enhanced micronucleus formation in bone marrow of tumorous rats is described. The cytogenetic effect of the hydrophobic (XAD-4) urinary fraction, which has been found to be mutagenic in the TA98 Salmonella strain, was examined in CBA mice. Sister chromatid exchange (SCE) analyses were performed on bone marrow cells of animals treated with single injections of concentrated urine samples. Significant and continuous increases could be detected in the SCE frequencies caused by the urinary concentrates with development of the tumour. Pseudouridine, a suggested urinary tumour marker nucleoside, was also studied for mutagenicity in the Ames Salmonella test. Both derivatives (alpha and beta), however, failed to induce mutations in the TA98/TA100 strains, either with or without metabolic activation. In conclusion, urinary mutagen(s) produced during the renal tumour growth have a spectrum of genotoxicity involving at least two endpoints, but the high pseudouridine excretion may not be responsible for these effects.